The collegiate church was built in the years 1587 – 1598, according to the project by an Italian architect, Bernardo Morando. It was endowed by the city founder, the Great Chancellor of the Crown, Jan Zamoysky.

The finishing works lasted until the first half of the 17th century. The Cathedral was consecrated in 1637. This splendid, slenderly proportioned temple with its barrel vault with lunettes and geometrically-shaped embellished stucco, became a model to be imitated in the sacral architecture in the first half of the 17th century. The building was crucial in the process of shaping the specific type of late-Renaissance architecture, referred to as the Lublin Renaissance. In the floor of the Chapel of Transfiguration of Jesus, also referred to as the Ordynacka Chapel or the Chapel of the Zamoyski family, there is a tombstone of Jan Zamoyski, under which his ashes are buried.

In 1992, when the zamojsko-lubaczowska diocese was established, the temple was designated as a cathedral.